N-acetylcysteine improves function and follicular survival in mice ovarian grafts through inhibition of oxidative stress

Abstract

The effect of N-acetylcysteine (NAC) on mouse ovary heterotopic autotransplantation was investigated. Mice (age 4-5 weeks) were divided into the following groups: control; autograft plus NAC (150 mg/kg daily intraperitoneal injection) and autograft plus saline (n = 6 per group). Groups were treated from 1 day before until 7 days after transplantation. After 28 days, ovary compartments were estimated stereologically. Plasma malondialdehyde, progesterone, oestradiol concentrations and the percentage of apoptotic follicles were measured to evaluate the rate of oxidative stress and ovarian graft function. The mean total volume of ovary, cortex and the number of follicles was significantly higher (all P < 0.001) in the autografts plus NAC group compared with the saline group. In the autografts plus NAC group, the mean percentage of apoptotic follicles (P < 0.001) and malondialdehyde concentration (P < 0.001 day 7; P < 0.05 day 28) were significantly lower, whereas oestradiol concentration was significantly higher (P < 0.05) compared with the saline group. Although NAC cannot compensate the above parameters to the control level, it considerably improves follicular survival and development and also the structure and function of transplanted ovaries, through reducing oxidative stress and apoptosis.

Remote Ischemic Preconditioning and N-Acetylcysteine in Autologous Ovarian Transplantation in Rats.

“…This substance is a tiol of low molecular weight derivated of cysteine and acts removing reactive oxygen species, in addition to improving nitric oxide activity and regulating microcirculation [12].…”

“…Meanwhile, treatment with NAC resulted in a higher number of secondary follicles compared with the GTx and R-IPC groups, through preventing initial tissue degeneration and follicle atresia as a result of its ability to delay or inhibit apoptosis of ovary cells in the time of hypoxia and also to reduce the ischemia-reperfusion injury through its antioxidant ability and increasing the glutathione reservoir [12].…”

“…However, Mahmoodi et al (2015) [12] postulated that the treatment with n-acetylcisteine actually improved estradiol concentration at the 28 ℎ postoperative day because of its anti-oxidant properties, these discordant results might be explained by the difference on treatment protocol used (lower doses administered for a longer period) or variations in hormone measurements induced by natural animal diversity or by environmental stress or handling, that could have led to inconclusive results.…”

“…This could be explained because in the first days of transplantation, granulosa cells and oocytes, particularly in developing follicles, undergo apoptosis as a result of ischemia and reperfusion injury induced by free radicals and lipid peroxidation. This can lead to the degeneration and atresia of follicles and disruption in folliculogenesis and oogenesis, which eventually decreases the ovary volume and size and also the number of follicles [12].…”

Effects of n-acetylcysteine on ovarian tissue autografted intogranulation tissue compared to back muscle in rats

“…In addition, it has been proven that NAC can inhibit apoptosis and promote cell survival (27). Mahmoodi et al showed that NAC improves follicular survival in mice ovarian autografts into the BM by decreasing oxidative stress and apoptosis (25). Amorim et al also reported that subcutaneous injection of NAC at a high dose improves follicular survival of ovarian tissue grafted into a retroperitoneal position (28).…”